Abstract
One of the earliest manifestations of Alzheimers disease (AD) is the characteristic inability of affected individuals to form new memories. Memory impairment appears to significantly predate the death of nerve cells, implying that neuronal dysfunction is responsible for the pathophysiology of early stage AD. Mounting evidence now indicates that soluble oligomers of the amyloid-β peptide (Aβ) are the main neurotoxins that lead to early neuronal dysfunction and memory deficits in AD. Cyclic AMP (cAMP) is a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Among other actions, cAMP triggers the phosphorylation and activation of the cAMP responsive element binding protein (CREB), a transcription factor that regulates the expression of genes that are important for long-term memory. Here, we discuss recent evidence suggesting that cAMP enhancing compounds may find applications as neurocognitive enhancers in AD and in other neurological disorders, as well as possible roles of cAMP in the regulation of neuronal regeneration. In particular, we review recent results showing that low concentrations of 2,4-dinitrophenol (DNP) upregulate neuronal cAMP and tau levels, promote neurite outgrowth and neuronal differentiation and block the oligomerization and neurotoxicity of Aβ. Possible implications of these findings in the development of novel therapeutic approaches in AD are discussed.
Keywords: 2,4-dinitrophenol, cAMP responsive element binding protein, Neuritogenesis, brain-derived neurotrophic factor, cortical neuronal, PKA levels
Current Alzheimer Research
Title: Cyclic AMP Enhancers and Aβ Oligomerization Blockers as Potential Therapeutic Agents in Alzheimers Disease
Volume: 4 Issue: 3
Author(s): Fernanda G. De Felice, Ana Paula Wasilewska-Sampaio, Anna Carolina A. P. Barbosa, Flavia C.A. Gomes and Sergio T. Ferreira
Affiliation:
Keywords: 2,4-dinitrophenol, cAMP responsive element binding protein, Neuritogenesis, brain-derived neurotrophic factor, cortical neuronal, PKA levels
Abstract: One of the earliest manifestations of Alzheimers disease (AD) is the characteristic inability of affected individuals to form new memories. Memory impairment appears to significantly predate the death of nerve cells, implying that neuronal dysfunction is responsible for the pathophysiology of early stage AD. Mounting evidence now indicates that soluble oligomers of the amyloid-β peptide (Aβ) are the main neurotoxins that lead to early neuronal dysfunction and memory deficits in AD. Cyclic AMP (cAMP) is a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Among other actions, cAMP triggers the phosphorylation and activation of the cAMP responsive element binding protein (CREB), a transcription factor that regulates the expression of genes that are important for long-term memory. Here, we discuss recent evidence suggesting that cAMP enhancing compounds may find applications as neurocognitive enhancers in AD and in other neurological disorders, as well as possible roles of cAMP in the regulation of neuronal regeneration. In particular, we review recent results showing that low concentrations of 2,4-dinitrophenol (DNP) upregulate neuronal cAMP and tau levels, promote neurite outgrowth and neuronal differentiation and block the oligomerization and neurotoxicity of Aβ. Possible implications of these findings in the development of novel therapeutic approaches in AD are discussed.
Export Options
About this article
Cite this article as:
Fernanda G. De Felice , Ana Paula Wasilewska-Sampaio , Anna Carolina A. P. Barbosa , Flavia C.A. Gomes and Sergio T. Ferreira , Cyclic AMP Enhancers and Aβ Oligomerization Blockers as Potential Therapeutic Agents in Alzheimers Disease, Current Alzheimer Research 2007; 4 (3) . https://dx.doi.org/10.2174/156720507781077287
DOI https://dx.doi.org/10.2174/156720507781077287 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Polypharmacological Drugs in the Treatment of Epilepsy: The Comprehensive Review of Marketed and New Emerging Molecules
Current Pharmaceutical Design Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases
Current Drug Targets Recent Evidence of the Regulatory Role of PPARs in Neural Stem Cells and Their Underlying Mechanisms for Neuroprotective Effects
Current Stem Cell Research & Therapy Non-Genotoxic p53-Activators and their Significance as Antitumor Therapy of Future
Current Medicinal Chemistry Impact of Hybrid-polar Histone Deacetylase Inhibitor m-Carboxycinnamic Acid bis-Hydroxyamide on Human Pancreatic Adenocarcinoma Cells
Anti-Cancer Agents in Medicinal Chemistry P2X7 Receptors: Channels, Pores and More
CNS & Neurological Disorders - Drug Targets Cannabinoids and Sensory Neurones
Current Neuropharmacology Transferrin and the Transferrin Receptor: Of Magic Bullets and Other Concerns
Inflammation & Allergy - Drug Targets (Discontinued) Highly Selective MEK Inhibitors
Current Enzyme Inhibition Genetic Editing and Pharmacogenetics in Current And Future Therapy Of Neurocognitive Disorders
Current Alzheimer Research Spirulina paltensis: Food and Function
Current Nutrition & Food Science Glucose Oncometabolism of Esophageal Cancer
Anti-Cancer Agents in Medicinal Chemistry Lipid Rafts Mediate Amyloid-Induced Calcium Dyshomeostasis and Oxidative Stress in Alzheimer’s Disease
Current Alzheimer Research Ignored Avenues in Alpha-Synuclein Associated Proteopathy
CNS & Neurological Disorders - Drug Targets The Vitamin D/CYP24A1 Story in Cancer
Anti-Cancer Agents in Medicinal Chemistry MiR-340 Reduces the Accumulation of Amyloid-β Through Targeting BACE1 (β-site Amyloid Precursor Protein Cleaving Enzyme 1) in Alzheimer’s Disease
Current Neurovascular Research Subject Index to Volume 10
Current Pharmaceutical Design The Therapeutic Value of Natural Agents to Treat miRNA Targeted Breast Cancer in African-American and Caucasian-American Women
Current Drug Targets Withania somnifera Phytochemicals Confer Neuroprotection by Inhibition of the Catalytic Domain of Human Matrix Metalloproteinase-9
Letters in Drug Design & Discovery Epigenetic control of cardiovascular health by nutritional polyphenols involves multiple chromatin-modifying writer-reader-eraser proteins
Current Topics in Medicinal Chemistry